The Women’s Health Initiative (WHI), a landmark study among 161,808 postmenopausal women that has been ongoing for more than 40 years, continues to contribute a wealth of insights towards the advancement of the science of nutrition. A special issue of the Journal of the Academy of Nutrition and Dietetics (JAND) on the Women’s Health Initiative, published by Elsevier, reviews the history of the WHI and adds to the body of knowledge, aiming to improve health through research on risk factors, prevention, and early detection of serious health conditions in postmenopausal women.

Co-Guest Editor Yasmin Mossavar-Rahmani, PhD, RDN, CDN, Division of Health Behavior Research and Implementation Science, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, says, “This special issue celebrates the contribution of the WHI to the field of nutrition and dietetics. JAND has chronicled findings from the WHI, publishing more than 32 related articles contributing to the evolving science of nutrition in this area. WHI is one of the largest studies on postmenopausal women in the United States and should be viewed as a national treasure.”

Editor-in-Chief of JAND, Linda G. Snetselaar, PhD, RDN, FAND, LD, a professor in the Department of Epidemiology at the University of Iowa, who has been part of the WHI since its inception, adds, “The WHI is the most prominent randomized controlled trial ever done among women in the United States. WHI has provided and continues to support the nutrition field with an unprecedented resource that continues to contribute to women’s health, and JAND has been at the forefront of conveying WHI results to dietitians.”

The WHI began as a trans-National Institutes of Health (NIH) initiative in 1991 under the leadership of Dr. Bernadine Healy, the first female director of the NIH. The WHI program includes a multifaceted randomized controlled clinical trial among 68,132 participants and a companion prospective observational study among 93,676 participants. All participants were postmenopausal and in the age range 50 to 79 years at enrollment. The program is focused on improving health through research on risk factors, prevention, and early detection of serious health conditions in postmenopausal women.

WHI included a dietary modification trial (DMT), which was the largest and longest running dietary trial ever conducted among 48,835 postmenopausal women to explore whether a low-fat dietary pattern with increased fruits, vegetables, and grains reduce the risk of breast cancer, colorectal cancer, and heart disease.

Co-Guest Editor Ross L. Prentice, PhD, Emeritus Member and former Director of the Public Health Sciences Division, Fred Hutchinson Cancer Center, says, “One of the main findings of the DMT was that a significant reduction in breast cancer mortality was observed in the intervention group as a whole. Other notable aims of WHI were to assess the impact of the hormone replacement therapy and calcium/vitamin D clinical trials on reducing risks for heart disease and hip fractures respectively, among other goals. WHI research has already had an impact on women’s lives. There are an estimated 12,600 fewer cases of breast cancer each year in the United States as a result of the WHI hormone replacement therapy trial. Data from the study continue to provide useful information on women’s health, specifically healthy aging, and many other population science research areas.”

The special issue includes “Effect of Unfermented Soy Product Consumption on Blood Lipids in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.”

Lead investigator Lirong Guo, MD, School of Nursing, Department of Rehabilitation, Jilin University, Changchun, explains, “Our study of 29 randomized controlled trials involving 2,457 participants found that unfermented soy product consumption reduced total cholesterol and triglyceride and increased high-density lipoprotein cholesterol levels significantly in postmenopausal women. We therefore conclude that the consumption of unfermented soy products may be considered as a potential dietary approach to assist in the management of blood lipids in postmenopausal women.”

Another article, “Diet Quality and Epigenetic Aging in the Women’s Health Initiative,” assessed whether diet quality is associated with aging biology among postmenopausal American women. Commenting on the findings of the study, lead investigator Lindsay M. Reynolds, PhD, Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake, Forest University School of Medicine, says, “Individuals with higher diet quality had significantly lower biological age as measured by epigenetic clocks than individuals with poorer diet quality, within a subset of the Women’s Health Initiative cohort.”

JAND has been covering the WHI for more than 40 years:

• 1993-2004:
  • Papers focused on the study protocol and preliminary findings.
  • Articles highlighted the value of motivating, rather than persuading, individuals to adopt healthier eating styles.
• 2004-2019:
  • A shift in focus to the results of the interventions and studies beyond diet.
  • Topics ranged from diet to psychosocial aspects to cost-effectiveness of the interventions.
• 2020-present:
  • New topics such as precision nutrition; dietary components that can benefit health specific to an individual’s profile at the molecular level.
  • Super aging: there are currently 12,623 participants of 90 years or older in the Long-Life Study being followed in WHI.

Looking at possible avenues for future research, Dr. Mossavar-Rahmani, notes, “There is the opportunity to study the environment (e.g., pollutants and home environment) and perhaps even the offspring generation. Can a healthy diet mitigate the effects of pollutants? What diet is best to prevent hearing loss or preserve eyesight? Looking at all the data simultaneously (i.e., physical activity, emotions, diet, cognition, and environment) and using ecological momentary assessment are other future areas to explore that could provide a more holistic understanding of the context.”